Monolithic integrated light-emitting-diode/photodetector sensor for photoactive analyte monitoring: design and simulation.

We present the simulation and design optimization of an integrated light-emitting-diode/photodetector (LED-PD) sensor system for monitoring of light absorbance changes developing in analyte-sensitive compounds. The sensor integrates monolithically both components in a single chip, offering advantages such as downsizing, reduced assembly complexity, and lower power consumption. The changes in the optical parameters of the analyte-sensitive ink are detected by monitoring the power transmission from the LED to the PD. Ray tracing and coupled modeling approach (CMA) simulations are employed to investigate the interaction of the emitted light with the ink. In highly absorbing media, CMA predicts more accurate results by considering evanescent waves. Simulations also suggest that an approximately 39% change in optical transmission can be achieved by adjusting the ink-deposited layer thickness and varying the extinction coefficient from 10-4 to 3×10-4.

Differential thermal analysis techniques as a tool for preliminary examination of catalyst for combustion.

The need for more economical catalysts for various combustion reactions is continuously driving catalyst development. We present Differential Thermal Analysis (DTA) and Differential Scanning Calorimetry (DSC) as suitable techniques for fast examination of catalyst activity for combustion reactions. The heat of reaction ΔHr generated at the catalyst in a combustible atmosphere is the measure for estimating the capability of the catalyst. Present investigations verify the reliability of both methods for the pre-selection of catalysts for further extensive investigations. To simplify the measurements and the result evaluation, a new measurement routine is introduced which is more suitable for rapid catalyst investigation than the conventional approach. For initial investigations, oxidation of 1% methane on a cobalt oxide catalyst was used. First, DTA measurements were performed. The vessel size and the amount of catalyst are considered as factors influencing the thermal signal. Simultaneous mass spectrometry measurements were used to better understand the formation of the DTA response. Comparable DSC investigations were then conducted. Finally, the behavior of catalyst was compared with two commercial palladium/alumina catalysts using DTA and DSC. Our investigations show that DTA and DSC are powerful methods to identify potential catalysts in a fast and reproducible manner, provided that all parameters influencing the thermal signal are kept constant.

Mitochondrial DNA Variation Contributes to the Aptitude for Dressage and Show Jumping Ability in the Holstein Horse Breed.

Maternal lineages are considered an important factor in breeding. Mitochondrial DNA (mtDNA) is maternally inherited and plays an important role in energy metabolism. It has already been associated with energy consumption and performances, e.g., stamina in humans and racehorses. For now, corresponding studies are lacking for sport performance of warmblood breeds. MtDNA sequences were available for 271 Holstein mares from 75 maternal lineages. As all mares within a lineage showed identical haplotypes regarding the non-synonymous variants, we expanded our data set by also including non-sequenced mares and assigning them to the lineage-specific haplotype. This sample consisting of 6334 to 16,447 mares was used to perform mitochondrial association analyses using breeding values (EBVs) estimated on behalf of the Fédération Équestre Nationale (FN) and on behalf of the Holstein Breeding Association (HOL). The association analyses revealed 20 mitochondrial SNPs (mtSNPs) significantly associated with FN-EBVs and partly overlapping 20 mtSNPs associated with HOL-EBVs. The results indicated that mtDNA contributes to performance differences between maternal lineages. Certain mitochondrial haplogroups were associated with special talents for dressage or show jumping. The findings encourage to set up innovative genetic evaluation models that also consider information on maternal lineages.

Exploring the Origin and Relatedness of Maternal Lineages Through Analysis of Mitochondrial DNA in the Holstein Horse.

Maternal lineages are important for the breeding decision in the Holstein horse breed. To investigate the genetic diversity of the maternal lineages and the relationships between founder mares, the maternal inherited mitochondrial genome (except the repetitive part of the non-coding region) of 271 mares representing 75 lineages was sequenced. The sequencing predominantly revealed complete homology in the nucleotide sequences between mares from one lineage with exceptions in 13 lineages, where differences in one to three positions are probably caused by de novo mutations or alternate fixation of heteroplasmy. We found 78 distinct haplotypes that have not yet been described in other breeds. Six of these occurred in two or three different lineages indicating a common ancestry. Haplotypes can be divided into eight clusters with all mares from one lineage belonging to the same cluster. Within a cluster, the average number of pairwise differences ranged from zero to 16.49 suggesting close maternal relationships between these mares. The results showed that the current breeding population originated from at least eight ancestral founder mares.

Screen-Printed Sensors for Colorimetric Detection of Hydrogen Sulfide in Ambient Air.

A fast and sensitive method to monitor hydrogen sulfide (H2S) in ambient air based on a visible color change of a printed disposable sensor has been developed. As gas-sensitive material, an immobilized copper(II) complex of the azo dye 1-(2-pyridylazo)-2-naphtol (H-PAN) was synthesized and prepared in an ethyl cellulose matrix for screen printing. If H2S is present in ambient air, the gas sensitive layer changes its color from purple to yellow. A pre-primed polyethylene (PE) foil and a coated offset paper served as the printing substrate. The colorimetric response to the target gas was measured by UV/Vis spectroscopy in reflection at H2S concentrations between 1 to 20 ppm. Possible cross-sensitivities of the printed sensors towards methane (CH4), formaldehyde (CH2O), carbon monoxide (CO), ammonia (NH3), and nitrogen dioxide (NO2), as well as the long-term stability was investigated. Furthermore, reflection measurements of the Cu-PAN complex on an amorphous silica powder under gas admission served as preliminary test for the subsequent paste development.

A sensitive assay reveals structural requirements for α-synuclein fibril growth.

The accumulation of α-synuclein (α-syn) fibrils in neuronal inclusions is the defining pathological process in Parkinson's disease (PD). A pathogenic role for α-syn fibril accumulation is supported by the identification of dominantly inherited α-syn (SNCA) gene mutations in rare cases of familial PD. Fibril formation involves a spontaneous nucleation event in which soluble α-syn monomers associate to form seeds, followed by fibril growth during which monomeric α-syn molecules sequentially associate with existing seeds. To better investigate this process, we developed sensitive assays that use the fluorescein arsenical dye FlAsH (fluorescein arsenical hairpin binder) to detect soluble oligomers and mature fibrils formed from recombinant α-syn protein containing an N-terminal bicysteine tag (C2-α-syn). Using seed growth by monomer association (SeGMA) assays to measure fibril growth over 3 h in the presence of C2-α-syn monomer, we observed that some familial PD-associated α-syn mutations (i.e. H50Q and A53T) greatly increased growth rates, whereas others (E46K, A30P, and G51D) decreased growth rates. Experiments with wild-type seeds extended by mutant monomer and vice versa revealed that single-amino acid differences between seed and monomer proteins consistently decreased growth rates. These results demonstrate that α-syn monomer association during fibril growth is a highly ordered process that can be disrupted by misalignment of individual amino acids and that only a subset of familial-PD mutations causes fibril accumulation through increased fibril growth rates. The SeGMA assays reported herein can be utilized to further elucidate structural requirements of α-syn fibril growth and to identify growth inhibitors as a potential therapeutic approach in PD.

Hand Sensibility, Strength, and Laxity of High-Level Musicians Compared to Nonmusicians.

PURPOSE: To determine whether musicians have more sensitive, stronger, and flexible hands than nonmusicians. METHODS: A total of 100 musicians and 100 control subjects were assessed for 2-point discrimination, Semmes-Weinstein monofilament light touch, grip and pinch strength, and laxity. Musicians were included if enrolled as instrumental performance majors at a 4-year accredited conservatory of music. Nonmusician controls were university students who never or rarely engaged in playing an instrument. All subjects were between the ages of 18 and 28. The exclusion criterion was history of any hand condition, trauma, surgery, or diabetes. Statistical analyses were carried out using the t test, analysis of variance, and correlation coefficients as appropriate. RESULTS: High-level musicians in our cohort showed the same handedness (dominance) as the general population. The musicians were weaker than the nonmusicians. Male musicians were significantly weaker in pinch and grip bilaterally than nonmusicians, whereas female musicians were significantly weaker only in grip on the right/dominant side. Two-point discrimination was significantly less in musicians for the left/nondominant index, ring, and small fingers, and the right/dominant small and dominant index finger. Semmes-Weinstein testing was significantly better for the right/dominant digits, including the thumb, but not the left digits with the exception of the ring and nondominant middle and ring. There was no difference in laxity between the 2 groups. CONCLUSIONS: High-level musicians have, in general, more sensitive but weaker hands than nonmusicians, but the differences seem small and may not be clinically important.

Synthesis and in vitro evaluation of α-synuclein ligands.

Accumulation of misfolded α-synuclein in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson's disease (PD). To identify ligands having high binding potency toward aggregated α-synuclein, we synthesized a series of phenothiazine derivatives and assessed their binding affinity to recombinant α-synuclein fibrils using a fluorescent thioflavin T competition assay. Among 16 new analogues, the in vitro data suggest that compound 11b has high affinity to α-synuclein fibrils (K(i)=32.10 ± 1.25 nM) and compounds 11d, 16a and16b have moderate affinity to α-synuclein fibrils (K(i)≈50-100 nM). Further optimization of the structure of these analogues may yield compounds with high affinity and selectivity for aggregated α-synuclein.

Catalytic function of PLA2G6 is impaired by mutations associated with infantile neuroaxonal dystrophy but not dystonia-parkinsonism.

BACKGROUND: Mutations in the PLA2G6 gene have been identified in autosomal recessive neurodegenerative diseases classified as infantile neuroaxonal dystrophy (INAD), neurodegeneration with brain iron accumulation (NBIA), and dystonia-parkinsonism. These clinical syndromes display two significantly different disease phenotypes. NBIA and INAD are very similar, involving widespread neurodegeneration that begins within the first 1-2 years of life. In contrast, patients with dystonia-parkinsonism present with a parkinsonian movement disorder beginning at 15 to 30 years of age. The PLA2G6 gene encodes the PLA2G6 enzyme, also known as group VIA calcium-independent phospholipase A(2), which has previously been shown to hydrolyze the sn-2 acyl chain of phospholipids, generating free fatty acids and lysophospholipids. METHODOLOGY/PRINCIPAL FINDINGS: We produced purified recombinant wildtype (WT) and mutant human PLA2G6 proteins and examined their catalytic function using in vitro assays with radiolabeled lipid substrates. We find that human PLA2G6 enzyme hydrolyzes both phospholipids and lysophospholipids, releasing free fatty acids. Mutations associated with different disease phenotypes have different effects on catalytic activity. Mutations associated with INAD/NBIA cause loss of enzyme activity, with mutant proteins exhibiting less than 20% of the specific activity of WT protein in both lysophospholipase and phospholipase assays. In contrast, mutations associated with dystonia-parkinsonism do not impair catalytic activity, and two mutations produce a significant increase in specific activity for phospholipid but not lysophospholipid substrates. CONCLUSIONS/SIGNIFICANCE: These results indicate that different alterations in PLA2G6 function produce the different disease phenotypes of NBIA/INAD and dystonia-parkinsonism. INAD/NBIA is caused by loss of the ability of PLA2G6 to catalyze fatty acid release from phospholipids, which predicts accumulation of PLA2G6 phospholipid substrates and provides a mechanistic explanation for the accumulation of membranes in neuroaxonal spheroids previously observed in histopathological studies of INAD/NBIA. In contrast, dystonia-parkinsonism mutations do not appear to directly impair catalytic function, but may modify substrate preferences or regulatory mechanisms for PLA2G6.

Developmental cues and persistent neurogenic potential within an in vitro neural niche.

BACKGROUND: Neurogenesis, the production of neural cell-types from neural stem cells (NSCs), occurs during development as well as within select regions of the adult brain. NSCs in the adult subependymal zone (SEZ) exist in a well-categorized niche microenvironment established by surrounding cells and their molecular products. The components of this niche maintain the NSCs and their definitive properties, including the ability to self-renew and multipotency (neuronal and glial differentiation). RESULTS: We describe a model in vitro NSC niche, derived from embryonic stem cells, that produces many of the cells and products of the developing subventricular zone (SVZ) and adult SEZ NSC niche. We demonstrate a possible role for apoptosis and for components of the extracellular matrix in the maintenance of the NSC population within our niche cultures. We characterize expression of genes relevant to NSC self-renewal and the process of neurogenesis and compare these findings to gene expression produced by an established neural-induction protocol employing retinoic acid. CONCLUSIONS: The in vitro NSC niche shows an identity that is distinct from the neurally induced embryonic cells that were used to derive it. Molecular and cellular components found in our in vitro NSC niche include NSCs, neural progeny, and ECM components and their receptors. Establishment of the in vitro NSC niche occurs in conjunction with apoptosis. Applications of this culture system range from studies of signaling events fundamental to niche formation and maintenance as well as development of unique NSC transplant platforms to treat disease or injury.